Platelet Fxn - Primary Hemostasis

Question 1

trigger for initiating clotting

Answer 1

injury induces transient vasoconstriction (endothelin release) and exposure of ECM

Question 2

von Willebrand factor (vWF) - sources, properties

Answer 2

secreted by endothelial cells onto ECM
secreted by megakaryocytes into circulation -> complexes with VIII
ligand for GPIbR on platelet filopodia

Question 3

describe platelet activation and aggregation

Answer 3

1) platelets bind to exposed vWF, undergo conformational change, expose phospholipid platform (accelerates fibrin production 100-1000x), release granules and TX A2

alpha granule: vWF, V, XIII, fibrinogen

delta granule: serotonin, ADP, Ca2+

2) ADP and TX A2 recruit platelets to aggregate
3) thrombin induces platelets form filopodia, link together by binding fibrinogen w/ GpIIb/IIIaRs
4) aggregation enhanced by thrombin, serotonin and epinephrine

Question 4

Reopro (abciximab)

Answer 4

monoclonal antibody
inhibits GpIIb/IIIaR
inhibits platelet plug formation

Question 5

Glanzmann thrombasthenia

Answer 5

inherited deficiency/dysfunction of GpIIb/IIIaR
platelet count and morphology normal
no response to epinephrine, ADP, collagen, arachidonic acid, or thrombin

Question 6

what is used as an anticoagulant in blood tubes?

Answer 6

sodium citrate

chelates Ca2+, a cofactor essential to multiple steps of the coagulation cascade

Question 7

blood collection for lab hemostasis studies - types, tests performed

Answer 7

blue top: contains sodium citrate; tests: prothrombin time (PT), activated partial thromboplastin time (a-PTT), factor VIII activity/antigen, individual factor assays, platelet aggregation, fibrinogen
QUALITATIVE STUDIES

purple top: contains EDTA; tests: platelets (quantitative), platelet aggregation studies
QUANTITATIVE STUDIES

red top: contains silica clot activator; test: clot retraction

Question 8

methods of primary hemostasis testing

Answer 8

bleeding time: measures time taken for standardized skin incision to stop bleeding; time-consuming, difficult to do well, not a good predictor of bleeding during hemostatic stresses
reference range: <5 min optimal
utility: detects vW disease and disorders of primary hemostasis

in-vitro testing for rare qualitative disorders of platelets

Question 9

von Willebrand disease

Answer 9

deficient/dysfunctional vWF or deficient/dysfunctional GpIaR

platelet count normal

Question 10

methods of secondary hemostasis testing

Answer 10

prothrombin time (PT): tests factors I, II, V, VII, and X; used to monitor defects in extrinsic pathway
coumadin test and vitamin K antagonist used for this, as well

activated partial thromboplastin time (a-PTT): used to measure defects in intrinsic pathway and heparin effect; cannot measure VII or XIII